The goals of this project are: (1) To understand mechanisms by which "molecular mimicry" between HIV-1 envelope (gp41) and human HLA class II antigens lead to generation of immunosuppressive cross-reactive anti-HLA antibodies (CRab) in infected individuals. (2) To measure the levels of cross-reactive anti-HLA class II antibodies in HIV-1 infected individuals in correlation with disease progression; (3) T determine if different classes of HIV-1 vaccines are capable of inducing deleterious anti-class II HLA antibodies in vaccinnees. We conducted several longitudinal studies of sera from patients enrolled in the MACS study. High correlation was found between the presence of CRab and rapid disease progression. Long term survivors do not produce such antibodies. We are also testing serum samples from multiple HIV vaccine groups (both therapeutic and phophylactic vaccines). Directly related to the safety of HIV envelope-based vaccines. The generation of autoantibodies with immunosuppressive potential will be of particular concern in immuno-compromised AIDS patients as well as in uninfected normal individuals.